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Uva ursi (Arctostaphylos uva-ursi)


Uva ursi (Arctostaphylos uva-ursi) Image
Synonyms / Common Names / Related Terms
Arberry, arbusier (French), arbutin, Arbutus uva ursi, arctostaphylos, Arctostaphylos adenotricha, Arctostaphylos coactilis, Arctostaphylos coactylis, Arctostaphylos uva-ursi, arctuvan, barentraube (German), bearberry, bear grape, bear's grape, bearsgrape, beerendruif (Holland), bousserole (French), common bearberry, common beargrape, coralillo (Spanish), creeping manzanita, crowberry, Cystinol akut®, Dunih'tan (Carrier people), Ericaceae (family), foxberry, gayuba (Spanish), hog berry, hydroquinone, kanya'ni, kwica (American Indian), kinnikinnick (American Indian), macnicy (Polish), manzanita, mealberry, mehlberre (German), melbaerblad (Norweigan), melbarrisblade (Danish), methyl arbutin, mjolonrisblad (Swedish), mossberre (German), mountain box, mountain cranberry, phenolic glycoside, ptarmigan berry, raisin d'ours (French), redberry, red bearberry, rock berry, rockberry, sagsckhomi (American Indian), sand berry, sandberry, Solvefort, s'qaya'dats, tannin, toloknianka (Russian), upland cranberry, Uroflux, uva d'orso (Italian), UVA-E, Uvae ursi folium, Uvalyst, uva-ursi, uva ursi leaf, whortle berry, wilder Buchsbaum (German), Wolfstraube (German).

Mechanism of Action

Pharmacology:

  • Constituents: Uva ursi leaves contain hydroquinone derivatives, mainly arbutin4,5 and methyl arbutin in concentrations ranging from 6.30 to 9.16%, expressed on a dry weight basis, depending on when and where it is harvested6. Tannins are also present in uva ursi leaves, including ellagic and gallic acid tannins, which can be hydrolyzed.7 Flavonoids that are present include hyperoside, myricetin, quercetin, and glycosides such as hyperin, myricitrin, isoquercitrin, and quercitrin. Triterpenes, montropein, piceoside, phenol-carboxylic acids such as alpha-amyrin and ursolic acids are present and also malic acid, allantoin, resin, volatile oil and wax. Uva ursi also contains corilagin.8
  • Anti-cancer properties: A study on mice demonstrated that ursolic acid, a constituent of uva ursi, may have beneficial effects on hematopoiesis and immunocompetance. The study results suggest that ursolic acid has the ability to decrease undesirable radiation damage to the hematopoietic tissue after radiotherapy.9
  • Anti-inflammatory properties: In an animal model of contact dermatitis, arbutin synergistically enhanced the anti-inflammatory properties of prednisolone in mice, while arbutin alone needed a dose of 100mg/kg or higher to produce significant therapeutic effects.2
  • Antimicrobial properties: Arbutin and extract from the leaves of uva ursi have inhibition effect on (-glucosidase activity of bacteria in vitro.10 The minimal bactericidal concentration of arbutin ranges from 0.4-0.8% depending on the species of microorganism.
  • Arbutin alone has been reported to be an effective urinary antibiotic, but only if taken in large doses and if the urine is alkaline. It is reported to be active against Candida albicans, Staphylococcus aureus and E. coli.11
  • An in vitro study indicated that aqueous extracts from bearberry leaves increased hydrophobicity of gram-negative bacteria (Escherichia coli and Acinetobactoer baumannii).12 Thus, the bacterial particles might be more easily aggregated and excreted.
  • In one double-blind study, uva ursi standardized extract was shown to be effective as prophylactic treatment in women with recurrent cystitis.13
  • A study on rats suggests that the disinfection action of uva ursi maybe beneficial for protection from urolithiasis, possibly due to the presence of saponins.14
  • Antitussive properties: A study in cats to determine the effectiveness of arbutin resulted in the ability of arbutin to suppress cough reflex induced by mechanical stimulation in unanesthized cats.15 The administration of 50mg/kg of body weight given by mouth or intraperitoneally was able to decrease the number of efforts, intensity of cough attack, and cough frequency significantly.
  • Antiviral properties: Ursolic acid, a constituent of uva ursi, demonstrated anti-HIV (human immunodeficiency virus) activity with EC50 4.4microM.16
  • Depigmentation properties: In vitro studies indicated that uva ursi was found to be effective in inhibiting melanin production.17
  • A human cell culture study shows that arbutin, a constituent of uva ursi, reduces melanin formation in melanocytes by inhibition of tyrosinase and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) polymerase activities.18
  • Another human cell culture study shows that the depigmentation effect of arbutin works through an inhibition of the melanosomal tyrosinase activity, rather than suppression of the expression and synthesis of tyrosinase in human melanocytes in vitro.19
  • Ursolic acid, a constituent of uva ursi, was shown to increase ceramide and collagen contents of cultured human epidermal and dermal cells.20
  • A study suggests that aloesin along with arbutin inhibits melanin production synergistically by noncompetitive and competitive inhibitions of tyrosinase activity.3
  • Diuretic properties: A study conducted in rats to evaluate the effects of the extract of uva ursi on diuretic activity resulted in an increase in urine flow.1
  • Endocrine properties: A study of diabetic mice concluded that uva ursi combined with a powdered diet reduced hyperphagia, polydipsia, although the effect of uva ursi was not maintained, and countered body weight loss.21
  • Ursolic acid, a constituent of uva ursi, seems to be a potent acetylcholinesterase (AchE) inhibitor.22
  • Immunological properties: An animal study suggests that hydroquinone inhibits B lineage cell maturation by interruption of macrophage production of IL-1.23

Pharmacodynamics/Kinetics:

  • Ursolic acid, a constituent of uva-uri, has an IC50 of 14.3microM and a therapeutic index of 3.3.16
  • Absorption: Arbutin, a constitiuent of uva ursi, is rapidly absorbed after oral administration.24
  • Excretion: Uva ursi extract has been shown to mark bile-expelling potency at a dose of 0.5g/kg.25
  • A crossover study on six healthy volunteers showed that arbutin equivalent (AE) concentration in the urine was 96% (CI = 80-120%), given gastric juice resistant coated tablets containing an extract of uva ursi folium (250mg tablets containing 50mg hydroquinone derivatives), compared to the water soluble extract.24 The release of AE was retarded for at least three hours while preserving the bioavailability in comparable values.
  • In a preliminary study with three healthy volunteers, more than half of the administered dose of arbutin was excreted within four hours mainly in form of the metabolites hydroquinone glucuronide and hydroquinone sulfate and more than 75% of the total applied arbutin was excreted within 24 hours.4 The elimination of hydroquinone was negligible in two out of three volunteers. The excretion of this metabolite in the third test person reached 5.6% of the total administered arbutin dose.
  • In a randomized crossover design in 16 healthy volunteers, the urinary excretion of arbutin metabolites was examined after ingestion of uva ursi extract as either a film-coated tablet or an aqueous solution.26 The total amounts of hydroquinone equivalents excreted in the urine from uva ursi leaf extract were similar in both groups. With film covered tablets, 64.8% of the arbutin dose administered was excreted; with aqueous solution, 66.7% was excreted (p=0.61). The maximum mean urinary concentration of hydroquinone equivalents was a little higher and peaked earlier in the aqueous solution group versus the film covered tablet group, although this did not reach statistical significance (Curmax=1.6893μmol/ml vs. 1.1250μmol/mL, p=0.13; tmax (t midpoint) = 3.60 hours vs. 4.40 hours, p=0.38). The relative bioavailability of film-covered tablets compared to the aqueous solution was 103.3% for total hydroquinone equivalents.

References

  1. Beaux D, Fleurentin J, Mortier F. Effect of extracts of Orthosiphon stamineus Benth, Hieracium pilosella L., Sambucus nigra L. and Arctostaphylos uva-ursi (L.) Spreng. in rats. Phytother Res 1999;13(3):222-225. 10353162
  2. Kubo M, Ito M, Nakata H, et al. [Pharmacological studies on leaf of Arctostaphylos uva-ursi (L.) Spreng. I. Combined effect of 50% methanolic extract from Arctostaphylos uva-ursi (L.) Spreng. (bearberry leaf) and prednisolone on immuno-inflammation]. Yakugaku Zasshi 1990;110(1):59-67. 1693958
  3. Jin YH, Lee SJ, Chung MH, et al. Aloesin and arbutin inhibit tyrosinase activity in a synergistic manner via a different action mechanism. Arch Pharm Res 1999;22(3):232-236. 10403123
  4. Quintus J, Kovar KA, Link P, et al. Urinary excretion of arbutin metabolites after oral administration of bearberry leaf extracts. Planta Med 2005;71(2):147-152. 15729623
  5. Kruszewska H, Zareba T, Tyski S. Examination of antimicrobial activity of selected non-antibiotic drugs. Acta Pol Pharm 2004;61 Suppl:18-21. 15909927
  6. Parejo I, Viladomat F, Bastida J, et al. A single extraction step in the quantitative analysis of arbutin in bearberry (Arctostaphylos uva-ursi) leaves by high-performance liquid chromatography. Phytochem Anal 2001;12(5):336-339. 11705262
  7. Wahner C, Schonert J, Friedrich H. [Knowledge of the tannin contained in leaves of the bearberry (Arctostaphylos uva-ursi L)]. Pharmazie 1974;29(9):616-617. 4473183
  8. Shimizu M, Shiota S, Mizushima T, et al. Marked potentiation of activity of beta-lactams against methicillin-resistant Staphylococcus aureus by corilagin. Antimicrob Agents Chemother 2001;45(11):3198-3201. 11600378
  9. Hsu HY, Yang JJ, Lin CC. Effects of oleanolic acid and ursolic acid on inhibiting tumor growth and enhancing the recovery of hematopoietic system postirradiation in mice. Cancer Lett 1997;111(1-2):7-13. 9022122
  10. Jahodár L, Jílek P, Páktová M, et al. [Antimicrobial action of arbutin and the extract from the leaves of Arctostaphylos uva-ursi in vitro]. Ceskoslov Farm 1985;34(5):174-178.
  11. Pizzorno J, Murry M. Textbook of Natural Medicine. 1999;989-990, 1187.
  12. Turi M, Turi E, Koljalg S, et al. Influence of aqueous extracts of medicinal plants on surface hydrophobicity of Escherichia coli strains of different origin. APMIS 1997;105(12):956-962. 9463514
  13. Larsson B, Jonasson A, Fianu S. Prophylactic effect of UVA-E in women with recurrent cystitis: a preliminary report. Current Therapeutic Research 1993;53(4):441-443.
  14. Grases F, Melero G, Costa-Bauza A, et al. Urolithiasis and phytotherapy. Int Urol Nephrol 1994;26(5):507-511. 7860196
  15. Strapkova A, Jahodar L, Nosal'ova G. Antitussive effect of arbutin. Pharmazie 1991;46(8):611-612. 1798722
  16. Kashiwada Y, Nagao T, Hashimoto A, et al. Anti-AIDS agents 38. Anti-HIV activity of 3-O-acyl ursolic acid derivatives. J Nat Prod 2000;63(12):1619-1622. 11141100
  17. Matsuda H, Higashino M, Nakai Y, et al. Studies of cuticle drugs from natural sources. IV. Inhibitory effects of some Arctostaphylos plants on melanin biosynthesis. Biol Pharm Bull 1996;19(1):153-156. 8820931
  18. Chakraborty AK, Funasaka Y, Komoto M, et al. Effect of arbutin on melanogenic proteins in human melanocytes. Pigment Cell Res 1998;11(4):206-212. 9711535
  19. Maeda K, Fukuda M. Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 1996;276(2):765-769. 8632348
  20. Yarosh DB, Both D, Brown D. Liposomal ursolic acid (merotaine) increases ceramides and collagen in human skin. Horm Res 2000;54(5-6):318-321. 11595826
  21. Swanston-Flatt SK, Day C, Bailey CJ, et al. Evaluation of traditional plant treatments for diabetes: studies in streptozotocin diabetic mice. Acta diabetol lat 1989;26:51-55.
  22. Chung YK, Heo HJ, Kim EK, et al. Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase. Mol Cells 2001;11(2):137-143. 11355692
  23. King AG, Landreth KS, Wierda D. Bone marrow stromal cell regulation of B-lymphopoiesis. II. Mechanisms of hydroquinone inhibition of pre-B cell maturation. J Pharmacol Exp Ther 1989;250(2):582-590. 2788217
  24. Paper DH, Koehler J, Franz G. Bioavailability of drug preparations containing a leaf extract of Arctostaphylos uva-ursi (L.) Spreng. (Uvae ursi folium). Pharmaceutical and Pharmacological Lett 1993;3:63-66.
  25. Azhunova TA, Sambueva ZG, Nikolaev SM, et al. [Bile-expelling effect of Arctostaphylos uva-ursi (L.) extract]. Farmatsiia 1988;37(2):41-43.
  26. Schindler G, Patzak U, Brinkhaus B, et al. Urinary excretion and metabolism of arbutin after oral administration of Arctostaphylos uvae ursi extract as film-coated tablets and aqueous solution in healthy humans. J Clin Pharmacol 2002;42(8):920-927. 12162475




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